{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:10:09Z","timestamp":1788786609352,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Osteoarthritis (OA) is biologically heterogeneous, and the relationship between MRI-detected inflammation and circulating innate immune activity remains uncertain. This study aimed to determine whether serum soluble Toll-like receptor 4 (sTLR4) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) distinguish between the study-specific MRI-defined INF-OA and non-INF-OA categories, and whether these biomarkers are associated with OA disease burden. Methods: This prospective, single-center, cross-sectional study included 30 patients with knee OA and 30 asymptomatic healthy controls. Patients with active OA flare-up, defined by a Knee Osteoarthritis Flare-Ups Score (KOFUS) \u2265 7, were excluded before MRI assessment and category assignment. Patients with OA were assigned to study-specific MRI-defined categories using MRI Osteoarthritis Knee Score (MOAKS) features: INF-OA (n = 16) required effusion-synovitis and\/or Hoffa-synovitis-related signal alteration graded \u2265 1, whereas non-INF-OA (n = 14) required grade 0 for both features. Biomarkers were measured by enzyme-linked immunosorbent assay. Primary within-OA biomarker comparisons were Holm-corrected, and adjusted models included age, sex, and body mass index (BMI). Results: Serum sTLR4 and sTREM-1 did not differ between INF-OA and non-INF-OA after Holm correction (adjusted p = 0.710 for both). In age-, sex-, and BMI-adjusted models, the INF-OA versus non-INF-OA geometric mean ratios were 1.15 (95% CI 0.92\u20131.44; p = 0.219) for sTLR4 and 1.09 (95% CI 0.89\u20131.35; p = 0.398) for sTREM-1. Given the modest within-OA subgroup sizes, smaller or moderate between-category differences cannot be excluded. After covariate adjustment, the overall OA cohort had higher geometric mean concentrations than controls for sTLR4 (ratio 1.85, 95% confidence interval 1.56\u20132.20; p &lt; 0.001) and sTREM-1 (ratio 1.67, 95% confidence interval 1.43\u20131.97; p &lt; 0.001). None of the systemic inflammatory measurements significantly distinguished INF-OA from non-INF-OA after correction for multiple comparisons. Within the OA cohort, each 1 ng\/mL increase in sTLR4 was associated with a 4.99-point higher Western Ontario and McMaster Universities Osteoarthritis Index total score after adjustment for age and body mass index (95% confidence interval 2.28\u20137.70; p &lt; 0.001). Conclusions: Circulating sTLR4 and sTREM-1 concentrations were higher in patients with OA than in asymptomatic healthy controls but did not distinguish the study-specific INF-OA and non-INF-OA categories in this sample. These findings should not be interpreted as evidence of biological equivalence between the MRI-defined categories. sTLR4 warrants further evaluation as a circulating correlate of current OA burden in larger longitudinal and multimodal studies.<\/jats:p>","DOI":"10.3390\/jcm15176902","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:12:25Z","timestamp":1788783145000},"page":"6902","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating sTLR4 and sTREM-1 in Knee Osteoarthritis: Associations with Study-Specific MRI-Defined Categories and Disease Burden"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9183-0250","authenticated-orcid":false,"given":"Ruhat","family":"\u00dcnl\u00fc","sequence":"first","affiliation":[{"name":"Department of Orthopedics and Traumatology, Istanbul Atlas University, Istanbul 34408, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1347-8498","authenticated-orcid":false,"given":"Hafize","family":"Uzun","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Istanbul Atlas University, Istanbul 34408, 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Mol. Diagn."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41584-024-01126-4","article-title":"Clinical Phenotypes, Molecular Endotypes and Theratypes in OA Therapeutic Development","volume":"20","author":"Mobasheri","year":"2024","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13075-017-1229-9","article-title":"Synovitis in Osteoarthritis: Current Understanding with Therapeutic Implications","volume":"19","author":"Mathiessen","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1007\/s00256-022-04191-6","article-title":"Structural Phenotypes of Knee Osteoarthritis: Potential Clinical and Research Relevance","volume":"52","author":"Roemer","year":"2023","journal-title":"Skelet. Radiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1186\/s13018-024-05194-w","article-title":"Association of MRI-Based Knee Osteoarthritis Structural Phenotypes with Short-Term Structural Progression and Subsequent Total Knee Replacement","volume":"19","author":"Liu","year":"2024","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.joca.2011.05.004","article-title":"Evolution of Semi-Quantitative Whole Joint Assessment of Knee OA: MOAKS (MRI Osteoarthritis Knee Score)","volume":"19","author":"Hunter","year":"2011","journal-title":"Osteoarthr. Cartil."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100602","DOI":"10.1016\/j.ocarto.2025.100602","article-title":"Imaging-Based Measures of Synovitis in Knee Osteoarthritis: A Scoping Review and Narrative Synthesis","volume":"7","author":"Dima","year":"2025","journal-title":"Osteoarthr. Cartil. Open"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100572","DOI":"10.1016\/j.ocarto.2025.100572","article-title":"The Inflammatory Endotype in Osteoarthritis: Reflections from the 2024 OARSI Clinical Trials Symposium (CTS) with a Special Emphasis on Feasibility for Clinical Development","volume":"7","author":"Karsdal","year":"2025","journal-title":"Osteoarthr. Cartil. Open"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jclinepi.2016.03.022","article-title":"Partial Verification Bias and Incorporation Bias Affected Accuracy Estimates of Diagnostic Studies for Biomarkers That Were Part of an Existing Composite Gold Standard","volume":"78","author":"Karch","year":"2016","journal-title":"J. Clin. Epidemiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/S0895-4356(03)00206-3","article-title":"Assessment of the Accuracy of Diagnostic Tests: The Cross-Sectional Study","volume":"56","author":"Knottnerus","year":"2003","journal-title":"J. Clin. Epidemiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4413","DOI":"10.1177\/0300060519860686","article-title":"Diagnostic Value of the Blood Monocyte\u2013Lymphocyte Ratio in Knee Osteoarthritis","volume":"47","author":"Gao","year":"2019","journal-title":"J. Int. Med. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1007\/s10067-016-3170-8","article-title":"Is Blood Neutrophil-Lymphocyte Ratio an Independent Predictor of Knee Osteoarthritis Severity?","volume":"35","year":"2016","journal-title":"Clin. Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100496","DOI":"10.1016\/j.ocarto.2024.100496","article-title":"Association of Peripheral Inflammatory Indicators with Osteoarthritis Risk","volume":"6","author":"Zhang","year":"2024","journal-title":"Osteoarthr. Cartil. Open"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"106145","DOI":"10.5312\/wjo.v16.i5.106145","article-title":"Role of Neutrophil to Lymphocyte Ratio in Osteoarthritis: A Systematic Review and Meta-Analysis","volume":"16","author":"Salimi","year":"2025","journal-title":"World J. Orthop."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1093\/rheumatology\/kead493","article-title":"Inhibition of TLR4 Signalling to Dampen Joint Inflammation in Osteoarthritis","volume":"63","author":"Bartels","year":"2024","journal-title":"Rheumatology"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lambert, C., Zappia, J., Sanchez, C., Florin, A., Dubuc, J.-E., and Henrotin, Y. (2021). The Damage-Associated Molecular Patterns (DAMPs) as Potential Targets to Treat Osteoarthritis: Perspectives From a Review of the Literature. Front. Med., 7.","DOI":"10.3389\/fmed.2020.607186"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41392-023-01330-w","article-title":"Osteoarthritis: Pathogenic Signaling Pathways and Therapeutic Targets","volume":"8","author":"Yao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1080\/17453674.2017.1281058","article-title":"Toll-like Receptors and Their Soluble Forms Differ in the Knee and Thumb Basal Osteoarthritic Joints","volume":"88","author":"Barreto","year":"2017","journal-title":"Acta Orthop."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1016\/j.joca.2018.08.005","article-title":"Biomarkers of Inflammation\u2014LBP and TLR\u2014Predict Progression of Knee Osteoarthritis in the DOXY Clinical Trial","volume":"26","author":"Huang","year":"2018","journal-title":"Osteoarthr. Cartil."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1002\/art.38315","article-title":"Gene Expression Pattern of Cells From Inflamed and Normal Areas of Osteoarthritis Synovial Membrane","volume":"66","author":"Lambert","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"L1377","DOI":"10.1152\/ajplung.00140.2007","article-title":"Functional Genomics of Silencing TREM-1 on TLR4 Signaling in Macrophages","volume":"293","author":"Ornatowska","year":"2007","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"933","DOI":"10.3899\/jrheum.111218","article-title":"Levels of Plasma-Soluble Triggering Receptor Expressed on Myeloid Cells-1 (STREM-1) Are Correlated with Disease Activity in Rheumatoid Arthritis","volume":"39","author":"Choi","year":"2012","journal-title":"J. Rheumatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"259","DOI":"10.4149\/BLL_2020_039","article-title":"A New Inflammatory Marker in Overweight Patients: Triggering Receptor Expressed on Myeloid Cells-1","volume":"121","author":"Cifci","year":"2020","journal-title":"Bratisl. Med. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1002\/art.1780290816","article-title":"Development of Criteria for the Classification and Reporting of Osteoarthritis: Classification of Osteoarthritis of the Knee","volume":"29","author":"Altman","year":"1986","journal-title":"Arthritis Rheum."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1161\/CIRCULATIONAHA.109.192644","article-title":"Harmonizing the Metabolic Syndrome","volume":"120","author":"Alberti","year":"2009","journal-title":"Circulation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1002\/art.42619","article-title":"The 2023 ACR\/EULAR Classification Criteria for Calcium Pyrophosphate Deposition Disease","volume":"75","author":"Abhishek","year":"2023","journal-title":"Arthritis Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1002\/art.39254","article-title":"2015 Gout Classification Criteria: An American College of Rheumatology\/European League Against Rheumatism Collaborative Initiative","volume":"67","author":"Neogi","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1002\/art.21972","article-title":"Classification Criteria for Psoriatic Arthritis: Development of New Criteria from a Large International Study","volume":"54","author":"Taylor","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1136\/ard.2010.133645","article-title":"The Assessment of SpondyloArthritis International Society Classification Criteria for Peripheral Spondyloarthritis and for Spondyloarthritis in General","volume":"70","author":"Rudwaleit","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1136\/ard.2009.108233","article-title":"The Development of Assessment of SpondyloArthritis International Society Classification Criteria for Axial Spondyloarthritis (Part II): Validation and Final Selection","volume":"68","author":"Rudwaleit","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1002\/art.40930","article-title":"2019 European League Against Rheumatism\/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus","volume":"71","author":"Aringer","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1002\/art.27584","article-title":"2010 Rheumatoid Arthritis Classification Criteria: An American College of Rheumatology\/European League Against Rheumatism Collaborative Initiative","volume":"62","author":"Aletaha","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.jbspin.2008.07.018","article-title":"Validation of the KOFUS (Knee Osteoarthritis Flare-Ups Score)","volume":"76","author":"Marty","year":"2009","journal-title":"Jt. Bone Spine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.2214\/AJR.08.2038","article-title":"Hoffa\u2019s Fat Pad: Evaluation on Unenhanced MR Images as a Measure of Patellofemoral Synovitis in Osteoarthritis","volume":"192","author":"Roemer","year":"2009","journal-title":"Am. J. Roentgenol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.joca.2016.09.016","article-title":"Comparison between Semiquantitative and Quantitative Methods for the Assessment of Knee Synovitis in Osteoarthritis Using Non-Enhanced and Gadolinium-Enhanced MRI","volume":"25","author":"Crema","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.joca.2004.10.010","article-title":"Acceptability, Reliability, Validity and Responsiveness of the Turkish Version of WOMAC Osteoarthritis Index","volume":"13","author":"Eker","year":"2005","journal-title":"Osteoarthr. Cartil."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zinellu, A., Collu, C., Nasser, M., Paliogiannis, P., Mellino, S., Zinellu, E., Traclet, J., Ahmad, K., Mangoni, A.A., and Carru, C. (2021). The Aggregate Index of Systemic Inflammation (AISI): A Novel Prognostic Biomarker in Idiopathic Pulmonary Fibrosis. J. Clin. Med., 10.","DOI":"10.3390\/jcm10184134"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6212","DOI":"10.1158\/1078-0432.CCR-14-0442","article-title":"Systemic Immune-Inflammation Index Predicts Prognosis of Patients after Curative Resection for Hepatocellular Carcinoma","volume":"20","author":"Hu","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1002\/cncr.30057","article-title":"A Novel Systemic Inflammation Response Index (SIRI) for Predicting the Survival of Patients with Pancreatic Cancer after Chemotherapy","volume":"122","author":"Qi","year":"2016","journal-title":"Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.joca.2025.08.019","article-title":"Does HsCRP Provide Insights into an Inflammatory Phenotype of Knee Osteoarthritis?","volume":"34","author":"George","year":"2026","journal-title":"Osteoarthr. Cartil."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e006011","DOI":"10.1136\/rmdopen-2025-006011","article-title":"Histological Synovitis and Radiographic Damage in Knee Osteoarthritis: Insights from a Comprehensive Analysis of Ultrasound-Guided Synovial Biopsies in 161 Patients","volume":"11","author":"Rubortone","year":"2025","journal-title":"RMD Open"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s13075-026-03819-5","article-title":"Revisiting Osteoarthritis as an Inflammatory Disease: Characterization of Synovitis Grading and Synovial Pathotypes in Surgical Specimens","volume":"28","author":"Ciaffi","year":"2026","journal-title":"Arthritis Res. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e063026","DOI":"10.1136\/bmjopen-2022-063026","article-title":"Minimal Important Change and Difference for Knee Osteoarthritis Outcome Measurement Tools after Non-Surgical Interventions: A Systematic Review","volume":"13","author":"Silva","year":"2023","journal-title":"BMJ Open"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1177\/1753425917726862","article-title":"Utility of Soluble Triggering Receptor Expressed on Myeloid Cells-1 (STREM-1) as Biomarker to Predict Therapeutic Response to Methotrexate in Rheumatoid Arthritis","volume":"23","year":"2017","journal-title":"Innate Immun."},{"key":"ref_45","first-page":"175","article-title":"Diagnostic Value of STREM-1 and Procalcitonin Levels in the Early Diagnosis of Sepsis","volume":"3","author":"Aksaray","year":"2016","journal-title":"North. Clin. Istanb."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.joca.2024.11.002","article-title":"Longitudinal Stability of Molecular Endotypes of Knee Osteoarthritis Patients","volume":"33","author":"Hannani","year":"2025","journal-title":"Osteoarthr. Cartil."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13075-026-03742-9","article-title":"Cytokine Profiling of Molecular Endotypes of Knee Osteoarthritis: Insights from the IMI-APPROACH Cohort","volume":"28","author":"Hannani","year":"2026","journal-title":"Arthritis Res. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1002\/acr.23698","article-title":"What Is the Evidence to Support the Association Between Metabolic Syndrome and Osteoarthritis? A Systematic Review","volume":"71","author":"Li","year":"2019","journal-title":"Arthritis Care Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1002\/art.40087","article-title":"Metabolic Syndrome, Its Components, and Knee Osteoarthritis: The Framingham Osteoarthritis Study","volume":"69","author":"Niu","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.joca.2015.01.013","article-title":"Diabetes Is a Risk Factor for Knee Osteoarthritis Progression","volume":"23","author":"Eymard","year":"2015","journal-title":"Osteoarthr. Cartil."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/17\/6902\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:39:47Z","timestamp":1788784787000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/17\/6902"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,6]]},"references-count":50,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jcm15176902"],"URL":"https:\/\/doi.org\/10.3390\/jcm15176902","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,6]]}}}